Trityl ethers, cleavage

De-O-tritylation. Trityl ether cleavage can be performed by treatment with CF3C(X)H-(CF3C0)20 without affecting other reducible and acid-hydrolyzable functionalities. 

Two groups have reported on the use of ZnBr2, either suspended in dichloromethane ° or in solution in nitromethane, as an aprotic reagent for trityl ether cleavage. 

The use of iodotrimethylsilane for this purpose provides an effective alternative to known methods. Thus the reaction of primary and secondary methyl ethers with iodotrimethylsilane in chloroform or acetonitrile at 25—60° for 2—64 hours affords the corresponding trimethylsilyl ethers in high yield. The alcohols may be liberated from the trimethylsilyl ethers by methanolysis. The mechanism of the ether cleavage is presumed to involve initial formation of a trimethylsilyl oxonium ion which is converted to the silyl ether by nucleophilic attack of iodide at the methyl group. tert-Butyl, trityl, and benzyl ethers of primary and secondary alcohols are rapidly converted to trimethylsilyl ethers by the action of iodotrimethylsilane, probably via heterolysis of silyl oxonium ion intermediates. The cleavage of aryl methyl ethers to aryl trimethylsilyl ethers may also be effected more slowly by reaction with iodotrimethylsilane at 25—50° in chloroform or sulfolane for 12-125 hours, with iodotrimethylsilane at 100—110° in the absence of solvent, " and with iodotrimethylsilane generated in situ from iodine and trimcthylphenylsilane at 100°. ... 

Furthermore, several functionalities remained unaffected, namely the acid-labile TBDMS or PMB groups.118 Deprotection yields were in the range of 85-95% when methanol was used at room temperature as the solvent, whereas acetonitrile or dichloromethane led to very sluggish or nonexistent reactions, respectively. Cleavage of primary trityl ethers was also accomplished using the same conditions in a very rapid and effective fashion. The trityl pyranosides and furanosides assayed were selectively deprotected in 2-3 h and yields higher than 85% were achieved. This reaction was also more efficient when conducted in methanol, which acts as a nucleophile to trap the generated trityl cation. 

Because of the high stability of the triphenylmethyl carbocation, the reductive ether cleavage of trityl ethers with EtySiH/trimethylsilyl triflate (TMSOTf) is highly successful. This reaction even occurs in the presence of highly reactive sugar ketals, leaving the ketals intact (Eq. 126).269... 

Detritylation. 1 Zinc bromide.is effective for removal of 5 -trityl ethers of deoxynuclcosides with only a slight effect on 3 -trityl ethers (cf. cleavage of MEM ethers, 7, 228). The reaction may involve chelation of ZnBr2 with the ether oxygen and the dcoxyribose ring oxygen. 

The introduction and cleavage of the trityl ether proceeds through a very well-stabilised triphenylmethyl carbocation. In the case of trityl ether bond formation, the reaction is performed under anhydrous conditions and the carbocation, which is formed by an SN1 mechanism, reacts with an alcohol. In the case of cleavage, the triphenylmethyl carbocation ion is formed by treatment with acid, which is then trapped by water or a nucleophilic solvent to give trityl alcohol or other derivatives, respectively. Trityl ethers have also been used to protect thiols. 

Cleavage of acid-labile protective groups.1 The reaction of H202 (70%, FMC) and CI3CCOOH in CH2C12/(-butyl alcohol converts a dimethyl acetal (1) into a hydroperoxy methyl acetal (a), which can be isolated but which for convenience (and safety) is reduced to the aldehyde 2 in 80% overall yield. The same conditions can effect oxidative cleavage of tetrahydropyranyl and trityl ethers. 

Cleavage of trityl ethers is accomplished by acid hydrolysis. Use of the mono- or di-methoxy analogs increase the acid lability of the trityl ethers, but none of the trityl ethers is stable enough to withstand normal glycosylation conditions, and they are only used as intermediates to construct building blocks to be used in subsequent oligosaccharide syntheses. 

Cleavage of the MOM group with dilute acids or with PPTS in r-BuOH regenerates the alcohol. A mild and selective reagent for removing the MOM group in the presence of methyl or benzyl ethers, -SiPh2 -Bu ethers, or esters is bromotrimethyl-silane. However, TMSBr will also cleave acetals and trityl ethers. ... 

Also the trityl group was applied for the masking of SH functions. The sulfides were prepared by the reaction of the thiol with trityl chloride (75% yield) or from trityl alcohol and the thiol in the presence of anhydrous TFA (85-90% yield). The cleavage of this group can be carried out under several conditions (Scheme 58). It is sensitive to acids (e.g. trifluoroacetic acid/ethanethiol 1 1) and to heavy metals. Thiocyanogen (SCN)2 oxidizes 5-trityl ethers to the disulfides and iodine converts 5-tritylcy -teine derivatives to cystine structures. 

Cleavage of a trUyl ether. The trityl ether (2) [6-0-trityl-l,2,3,4-tetra-0-acetyl-/3-D-glucose] was detritylated by adding a saturated solution of dry hydrogen bromide... 

Addition of lithium reagent derived from 355 to 382 produced a 1 1 mixture of adducts 363 in 75% yield. As this pro C-9 center will later be oxidized to the ketone, this mixture is of no consequence. LAH reduction of the propargyl alcohol followed by protection of the C-9 hydroxyl as the benzoate gave a 73% yield of the ( , )-diene 364. The primary and secondary alcohols, freed by cleavage of the acetonide, were protected as the trityl ether and benzoate, respectively, followed by desilylation to afford 365. The required two-carbon unit... 

CF3COOH, f-BuOH, 20"C, 2-30 min, then Bio-Rad lx2(OH ) resin. These conditions were used to cleave the trityl group from the 5 -hydroxyl of a nucleoside. Bio-Rad resin neutralizes the hydrolysis and minimizes cleavage of glycosyl bonds. TFA supported on silica gel will cleave trityl ethers (83-100% yield). ... 

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